Ca Stomach

Risk Factors of Gastric Cancer

Detailed Information on Risk Factors of Gastric Cancer

1. Overview: Gastric cancer, particularly adenocarcinoma, is influenced by a variety of risk factors, both environmental and genetic. Understanding these risk factors is crucial for prevention, early detection, and management of the disease.

2. Environmental Factors:

• Helicobacter pylori Infection:
  • Helicobacter pylori (H. pylori) is the most significant risk factor for gastric cancer. It leads to chronic gastric inflammation, which can progress through the Correa cascade (chronic gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → adenocarcinoma).
  • Virulence Factors: Strains with CagA and VacA virulence factors are particularly associated with a higher risk of gastric cancer due to their ability to induce severe inflammation and genetic alterations in the gastric mucosa.
• Dietary Factors:
  • High-Salt Diet: Consuming foods high in salt, especially salted or smoked meats containing nitrates, increases the risk of gastric cancer. Salt can damage the stomach lining, and nitrates can convert into carcinogenic N-nitroso compounds.
  • Low Intake of Fruits and Vegetables: A diet low in fresh fruits and vegetables, which are rich in antioxidants such as ascorbic acid, is linked to a higher risk of gastric cancer. These antioxidants help neutralize harmful free radicals and carcinogens.
  • Refrigeration: Increased use of refrigeration has reduced the need for salt preservation of foods, leading to a decline in gastric cancer rates over the past decades.

• Tobacco and Alcohol:

  • Tobacco Use: Smoking is a well-established risk factor for gastric cancer. Tobacco smoke contains N-nitroso compounds and other carcinogens that can damage the gastric mucosa.

  [ Alcohol is not associated with Gastric cancer]

• Previous Gastric Surgery:

  • Individuals who have undergone gastric surgery, such as partial gastrectomy for benign conditions, have an increased risk of developing gastric cancer due to changes in gastric anatomy and physiology, including bile reflux.

3. Genetic Factors:

• Family History:
  • A family history of gastric cancer significantly increases an individual's risk. This could be due to shared genetic factors or common environmental exposures within families.
• Hereditary Syndromes:
  • Hereditary Diffuse Gastric Cancer (HDGC): Caused by mutations in the CDH1 gene, which codes for the cell adhesion molecule E-cadherin. Individuals with this mutation have a 60-70% lifetime risk of developing diffuse gastric cancer. Prophylactic total gastrectomy is often recommended for carriers.
  • Familial Adenomatous Polyposis (FAP): Patients with FAP, caused by mutations in the APC gene, have an increased risk of gastric cancer, particularly in the form of fundic gland polyps.
  • Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer): Associated with mutations in mismatch repair genes (e.g., MLH1, MSH2), increasing the risk of gastric and other cancers.
  • Li-Fraumeni Syndrome: Caused by mutations in the TP53 gene, associated with a high risk of various cancers, including gastric cancer.
• Other Genetic Mutations:
  • Mutations in other genes, such as BRCA2, E-cadherin, and p53, have been associated with an increased risk of gastric cancer. Genetic testing and counseling are recommended for individuals with a strong family history of gastric cancer.

4. Additional Factors:

• Blood Type:
  • Individuals with blood type A are at a higher risk of developing gastric cancer compared to other blood types. The reasons for this association are not fully understood but may relate to genetic and immunologic factors.
• Socioeconomic Status:
  • Lower socioeconomic status is associated with a higher risk of gastric cancer. This may be due to differences in diet, higher prevalence of H. pylori infection, and limited access to healthcare and early detection services.

MCQ and Explanation:

Answer:A. H. pylori causes gastric cancer through Correa cycle

Explanation:

Epidemiology and Risk Factors:

• Helicobacter pylori is recognized as a significant risk factor for the development of gastric cancer. The infection leads to chronic inflammation which can progress through a sequence of precancerous lesions known as the Correa cascade: chronic gastritis, atrophic gastritis, intestinal metaplasia, dysplasia, and ultimately adenocarcinoma.
• H. pylori eradication has been shown to reduce the incidence of metachronous gastric cancer, especially after endoscopic resection of early gastric cancer.
• Eradication of H. pylori in individuals with a family history of gastric cancer has also been associated with a decreased risk of developing gastric cancer.
• A is correct (false) because although H. pylori infection is a significant risk factor for gastric cancer, the Correa cascade describes the general progression of gastric carcinogenesis rather than specifically attributing it to H. pylori. H. pylori initiates the inflammatory process, but the cascade can be influenced by various factors.
• B is true because eradication of H. pylori has been shown to prevent metachronous gastric cancer, particularly after the endoscopic resection of early gastric cancer.
• C is true because eradicating H. pylori in individuals with a family history of gastric cancer reduces their risk of developing the disease.
• D is incorrect because one of the statements (A) is false.

MCQ and Explanation:

Answer:D. Alcohol consumption

Explanation:

• A. Type A blood group: Individuals with blood type A are at a higher risk of developing gastric cancer. The reasons for this association are not fully understood but may relate to genetic and immunologic factors.
• B. BRCA 2 mutation: Mutations in BRCA2 are associated with an increased risk of gastric cancer. Genetic mutations in other genes, such as E-cadherin and p53, also contribute to the risk.
• C. MALT lymphoma: A history of mucosa-associated lymphoid tissue (MALT) lymphoma is a known risk factor for gastric cancer. H. pylori infection, which is associated with MALT lymphoma, also significantly increases the risk.
• D. Alcohol consumption: Although alcohol consumption is a risk factor for various types of cancer, it is not specifically mentioned in the provided context as a risk factor for gastric cancer.

Lauren Classification System for Gastric Cancer

MCQ and Explanation:

Answer:B and C

Explanation:

• A. Intestinal type occurs in presence of H. pylori infection: This statement is true. The intestinal type of gastric cancer is often associated with H. pylori infection, which leads to chronic inflammation and progresses through the Correa cascade.
• B. Intestinal type occurs in proximal body and fundus: This statement is not true. The intestinal type typically occurs in the distal portion of the stomach, such as the antrum.
• C. Diffuse variant occurs in distal body and antrum: This statement is not true. The diffuse variant usually affects the proximal part of the stomach, such as the body and cardia, and is known for its infiltrative growth pattern.
• D. E-cadherin mutation seen in diffuse variant: This statement is true. The diffuse variant of gastric cancer is often associated with mutations in the E-cadherin gene, which leads to a loss of cell adhesion and more aggressive tumor behavior.

Key Points:

• The Lauren classification system divides gastric adenocarcinomas into two types: intestinal and diffuse.
• Intestinal type is linked to environmental factors like H. pylori infection, with gland formation and frequent occurrence in the distal stomach.
• Diffuse type is associated with genetic factors such as E-cadherin mutations and tends to involve the proximal stomach with a more infiltrative growth pattern.

Genetic and Molecular Markers in Intestinal Gastric Cancer

Context from Background Knowledge

Intestinal gastric cancer is characterized by distinct genetic and molecular alterations. These include mutations and dysregulations in various oncogenes and tumor suppressor genes. Here's a brief overview of the key molecular markers involved in intestinal gastric cancer:

1. Beta-catenin: Beta-catenin is a protein involved in the Wnt signaling pathway, which is crucial for cell proliferation and differentiation. In many cancers, including intestinal gastric cancer, beta-catenin levels are often increased due to mutations in genes like APC (adenomatous polyposis coli).
2. APC: The APC gene is a tumor suppressor that regulates the Wnt signaling pathway by degrading beta-catenin. Mutations in APC are common in intestinal-type gastric cancer and lead to increased beta-catenin activity.
3. MSI (Microsatellite Instability): MSI is a condition of genetic hypermutability that results from impaired DNA mismatch repair. It is observed in various cancers, including intestinal gastric cancer.
4. TGF-alpha (Transforming Growth Factor-alpha): TGF-alpha is a growth factor that binds to the epidermal growth factor receptor (EGFR), promoting cell proliferation. It is often overexpressed in gastric cancer, contributing to tumorigenesis.
5. Bcl-2: Bcl-2 is an anti-apoptotic protein that prevents cell death, promoting cancer cell survival. Its expression can be upregulated in various cancers, including gastric cancer.

MCQ Explanation

Answer : A

Here's an analysis of each option:

• a. Decreased Beta-catenin: Intestinal gastric cancer often shows increased nuclear beta-catenin due to mutations in the APC gene or other components of the Wnt signaling pathway, leading to its stabilization and translocation to the nucleus. Therefore, decreased beta-catenin is indeed least likely.
• b. Heterozygosity of APC: The APC gene is commonly mutated in intestinal-type gastric cancer, resulting in the loss of function and disruption of the Wnt signaling pathway. Heterozygosity for APC is a typical feature.
• c. MSI (Microsatellite Instability): MSI is a well-documented phenomenon in various gastrointestinal cancers, including intestinal gastric cancer. It indicates a defect in the DNA mismatch repair system, which is quite common in these cancers.
• d. TGF alpha (Transforming Growth Factor-alpha): TGF-alpha is a growth factor that can be overexpressed in many cancers, including gastric cancer, promoting tumor growth and proliferation.
• e. Heterozygosity of Bcl-2: Bcl-2 is an anti-apoptotic protein, and alterations in its expression can contribute to cancer. However, Bcl-2 alterations are more commonly associated with other types of cancer, such as lymphomas, rather than being a primary characteristic of intestinal gastric cancer.

Linitis Plastica

Detailed Information on Linitis Plastica

Linitis plastica is a distinct and aggressive form of gastric cancer, typically falling under the diffuse variant of the Lauren classification. It is characterized by its extensive involvement of the stomach wall, leading to a thickened, rigid, and non-distensible stomach.

Key Points:

• Prevalence: Linitis plastica accounts for approximately 5% of all gastric cancers.
• Demographics: It is more commonly observed in younger patients and is associated with the diffuse type of gastric adenocarcinoma.
• Pathology: This variant is poorly differentiated and typically lacks gland formation, making it more challenging to detect through standard endoscopic techniques.
• Metastasis: There is a high frequency of nodal and peritoneal spread in patients with linitis plastica. In some rare cases, it may represent metastatic spread from lobular carcinoma of the breast.
• Diagnosis: Due to the diffuse infiltration of the stomach wall, endoscopic mucosal biopsy may often miss the diagnosis, as the tumor cells are located deeper in the submucosa or muscularis propria.
• Management: The standard treatment for linitis plastica includes total gastrectomy. Due to the aggressive nature of the disease, preoperative chemotherapy is often recommended, along with staging laparoscopy to evaluate for peritoneal disease.

MCQ and Explanation:

Answer:C. Diagnosis is by endoscopic mucosal biopsy

Explanation:

• A. Occurs in around 5% of all gastric cancer: This is true. Linitis plastica is a rare form of gastric cancer, accounting for approximately 5% of cases.
• B. Higher in younger individuals, diffuse type variant: This is true. Linitis plastica is associated with the diffuse variant of gastric adenocarcinoma, which tends to occur in younger individuals.
• C. Diagnosis is by endoscopic mucosal biopsy: This is false. The diagnosis of linitis plastica can be challenging with standard endoscopic mucosal biopsy because the cancer cells often infiltrate deep into the submucosa or muscularis propria, making them difficult to detect with superficial biopsies.
• D. Can represent metastatic spread from lobular cancer of the breast: This is true. Linitis plastica can, in rare cases, represent metastatic disease from lobular carcinoma of the breast.

Summary of Key Points on Linitis Plastica:

• 5% of all gastric cancer
• Poorly differentiated
• Young patients
• High frequency of nodal and peritoneal disease
• Require total gastrectomy
• Preoperative chemotherapy and staging lap recommended
• Rare cases represent metastasis from lobular breast cancer

Early Gastric Cancer (EGC)

Detailed Information on Early Gastric Cancer

Early Gastric Cancer (EGC) is defined by the depth of tumor invasion, not by the presence or absence of lymph node metastasis. It is generally confined to the mucosa or submucosa of the stomach, regardless of whether lymph nodes are involved.

1. Stages Classified as Early Gastric Cancer:

• EGC is characterized by cancer that invades up to the submucosa of the stomach wall, regardless of the presence of lymph node metastasis. This includes T1a (limited to the mucosa) and T1b (invasion into the submucosa) stages.

2. Rate of Lymph Node Spread in Early Gastric Cancer:

• Despite the superficial nature of EGC, lymph node metastasis can occur. The rate of lymph node involvement varies, but it is generally observed in about 10-20% of cases with submucosal invasion (T1b), and it is rare in cases confined to the mucosa (T1a).

3. Treatment Options:

• Endoscopic Mucosal Resection (EMR) and Endoscopic Submucosal Dissection (ESD):
  • EMR and ESD are minimally invasive procedures used to resect early gastric cancers that are confined to the mucosa or superficial submucosa.
  • Indications:
    • Small, well-differentiated tumors (generally ≤2 cm) confined to the mucosa (T1a) without ulceration or lymphovascular invasion.
    • Tumors with low risk of lymph node metastasis.
  • Contraindications:
    • Tumors with evidence of deep submucosal invasion (T1b) or larger size (>2 cm), particularly with ulceration.
    • Presence of lymph node positivity or high-risk histological features (poor differentiation, lymphovascular invasion).

4. Lymph Node Positivity and Surgical Intervention:

• If lymph node positivity is detected or if the tumor invades the deeper layers (T1b), endoscopic approaches like EMR or ESD are not appropriate. In such cases, the standard of care is surgical resection through gastrectomy, often with a D1 or D2 lymphadenectomy depending on the extent of nodal involvement.

5. Adjuvant or Neoadjuvant Therapy in Early Gastric Cancer:

• Patients with EGC typically do not require adjuvant or neoadjuvant therapy if the cancer is confined to the mucosa or superficial submucosa and has been completely resected with clear margins and no high-risk features. However, if there is lymph node involvement or other high-risk features, additional treatment may be considered.

MCQ and Explanation:

Answer:C. All early gastric cancer can be treated with endoscopic resection

Explanation:

• A. Invasion of submucosa irrespective of lymph node metastasis: This is true. EGC includes tumors that invade the submucosa (T1b) regardless of lymph node metastasis.
• B. Patients with early gastric cancer do not require adjuvant or neoadjuvant therapy: This is true in cases where the cancer is limited to the mucosa or superficial submucosa without high-risk features or lymph node involvement.
• C. All early gastric cancer can be treated with endoscopic resection: This is false. Not all cases of EGC are suitable for endoscopic resection. Tumors with submucosal invasion (T1b), lymph node positivity, or other high-risk features typically require surgical resection.
• D. All patients with early gastric cancer should be tested for H. pylori: This is true. Testing and eradicating H. pylori is recommended as it reduces the risk of metachronous gastric cancer.

Summary of Key Points on Early Gastric Cancer:

• Stages: T1a (mucosa) and T1b (submucosa) are classified as early gastric cancer.
• Lymph Node Spread: Lymph node metastasis occurs in about 10-20% of cases with submucosal invasion.
• Treatment Options: EMR and ESD are indicated for small, mucosa-confined, low-risk tumors. Gastrectomy is required if there is lymph node positivity or deeper invasion.
• Therapy: Adjuvant or neoadjuvant therapy is generally not required for low-risk, fully resected EGC.

Endoscopic Submucosal Dissection (ESD) for Early Gastric Cancer

Detailed Information on ESD Indications

Endoscopic Submucosal Dissection (ESD) is a minimally invasive procedure used to remove early gastric cancers that are confined to the mucosa or superficial submucosa. The indications for ESD can be divided into classical indications and expanded criteria.

1. Classical Indications for ESD:

• Tumor Characteristics:
  • Size: Tumors with a diameter less than 2 cm.
  • Ulceration: Tumors without ulceration.
  • Location: Tumors confined to the mucosa (T1a).
  • Differentiation: Tumors that are well-differentiated.

These criteria focus on small, well-differentiated tumors that are unlikely to have lymph node metastasis, making them suitable for endoscopic resection.

2. Expanded Criteria for ESD:

• Mucosal Tumors:
  • Any size, well-differentiated, without ulceration.
  • Less than 3 cm, well-differentiated, with ulceration.
  • Less than 2 cm, undifferentiated, without ulceration.
• Submucosal Tumors:
  • Less than 3 cm, well-differentiated, with SM1 involvement.

The expanded criteria allow for the inclusion of larger tumors and those with some degree of submucosal invasion (T1b) as long as they are well-differentiated and the invasion is limited (SM1), meaning minimal involvement in the submucosal layer. These tumors still have a low risk of lymph node metastasis, which justifies the use of ESD.

3. Limitations and Contraindications:

• Lymph Node Positivity: If lymph node metastasis is present, ESD is contraindicated. These cases require more extensive surgical approaches, such as gastrectomy with lymph node dissection.
• Tumor Size and Depth: Tumors larger than the criteria (e.g., submucosal tumors larger than 3 cm) are also not suitable for ESD due to the increased risk of lymph node metastasis.

MCQ and Explanation:

Answer:C & D

Explanation:

• A. Mucosal tumor, well differentiated, 2.5 cm with ulceration: This is within the expanded criteria for ESD, as it is a mucosal tumor less than 3 cm with ulceration.
• B. Mucosal tumor, 3 cm, well differentiated without ulceration: This fits within the expanded criteria for ESD and is an acceptable indication.
• C. Submucosal tumor 3.5 cm, well differentiated, SM1 involvement: This is not an indication for ESD because the tumor size exceeds 3 cm, which is outside the expanded criteria for submucosal tumors.
• D. Lymph node positive tumor: Lymph node positivity is a contraindication for ESD, requiring a more radical surgical approach.

Summary of Key Points on ESD Indications:

• Classical Indications:
  • Tumors less than 2 cm, well-differentiated, without ulceration, confined to the mucosa.
• Expanded Criteria:
  • Mucosal tumors of any size (if well-differentiated and without ulceration), less than 3 cm (with ulceration), and less than 2 cm (if undifferentiated and without ulceration).
  • Submucosal tumors less than 3 cm with SM1 involvement, well-differentiated.
• Contraindications:
  • Tumors larger than 3 cm (especially in the submucosa) and lymph node-positive tumors are not candidates for ESD.

Hereditary Diffuse Gastric Cancer (HDGC)

Detailed Information on Hereditary Diffuse Gastric Cancer

Hereditary Diffuse Gastric Cancer (HDGC) is a genetic condition characterized by a high risk of developing diffuse gastric cancer, often at a young age, and is associated with mutations in the CDH1 gene. This syndrome also increases the risk of other cancers, most notably lobular breast cancer in women.

Inheritance and Genetic Basis:

• 1% to 3% of gastric cancers are hereditary, with the most common type being Hereditary Diffuse Gastric Cancer (HDGC).
• Autosomal Dominant Inheritance: HDGC is inherited in an autosomal dominant manner, meaning that only one copy of the mutated gene is necessary to increase the risk of cancer.
• CDH1 Gene Mutation: The primary gene implicated in HDGC is CDH1, which encodes the protein E-cadherin. E-cadherin is crucial for cell-cell adhesion, and its loss leads to the loss of cellular cohesion, a hallmark of diffuse-type gastric cancer.
• Penetrance: The penetrance of the CDH1 mutation is high, with an estimated 70-80% lifetime risk of developing diffuse gastric cancer for mutation carriers. Additionally, women with this mutation have a 40-60% risk of developing lobular breast cancer.

Clinical Features and Pathology:

• Diffuse Gastric Cancer: Unlike the intestinal type of gastric cancer, which forms glandular structures, diffuse gastric cancer spreads through the stomach wall as individual cells, leading to thickening and rigidity of the stomach, often termed linitis plastica. This cancer is difficult to detect early because it does not form a distinct mass.
• Lobular Breast Cancer: Women with HDGC are also at increased risk for lobular breast cancer, which is another type of cancer characterized by the loss of E-cadherin expression.
• Histology: Diffuse signet ring cells are the hallmark of HDGC.

Screening and Surveillance:

• Indications for Screening:

  • Two or more cases of gastric cancer in a family, regardless of age, with at least one case being diffuse gastric cancer.
  • Diffuse gastric cancer diagnosed before age 40.
  • Diffuse gastric cancer plus lobular breast cancer, particularly if the breast cancer is diagnosed before age 50.
  • Expanded Indications:
    • Bilateral lobular breast cancer.
    • Cleft lip/palate in association with diffuse gastric cancer.
    • Signet ring cells detected on gastric biopsy.

Surveillance Biopsy:

• For individuals who do not opt for prophylactic gastrectomy, intensive surveillance with endoscopy is recommended. This involves taking at least 30 biopsies from different regions of the stomach, as the diffuse nature of the cancer makes it difficult to detect through routine biopsies.

Management:

• Prophylactic Gastrectomy:
  • Timing: Prophylactic total gastrectomy is recommended for asymptomatic carriers of the CDH1 mutation, typically between the ages of 18-40, before the cancer can develop.
  • Rationale: The procedure is recommended due to the high lifetime risk of diffuse gastric cancer and the difficulty in detecting early-stage disease. Prophylactic gastrectomy has been shown to be effective in preventing gastric cancer in mutation carriers.
• Breast Cancer Screening:
  • Women with HDGC should also undergo enhanced breast cancer screening starting at an earlier age. This may include regular mammograms, breast MRI, and in some cases, consideration of prophylactic mastectomy.
• Genetic Counseling:
  • Given the implications of the CDH1 mutation, genetic counseling is recommended for affected individuals and their families to discuss the risks, management options, and the potential for testing at-risk relatives.

Summary of Key Points on Hereditary Diffuse Gastric Cancer (HDGC):

• Inheritance: Autosomal dominant, linked to CDH1 gene mutations.
• Cancer Risk: 70-80% lifetime risk of diffuse gastric cancer, 40-60% risk of lobular breast cancer in women.
• Screening Indications: Family history of gastric cancer, especially diffuse type, and associated risk factors such as lobular breast cancer or cleft lip/palate.
• Prophylactic Gastrectomy: Recommended for mutation carriers between 18-40 years old.
• Surveillance: Involves extensive endoscopic biopsy (30 biopsies recommended) for those who defer surgery.

Staging and Management of Gastric Cancer

involvement of esophagus or duodenum is not considered T4b involvement of D2 duodenum is considered metastatic.

Case Scenario: Mr. CY

MCQ and Explanation

• Answer: B. pT3N3M0
• Explanation:
  • Tumor (T3): The tumor infiltrates the subserosal connective tissue, including the greater omentum, without breaching the visceral peritoneum.
  • Nodes (N3): Seven lymph nodes are positive for the tumor.
  • Metastasis (M0): No distant metastasis is present.

Gastric Cancer Based on Staging

Given the complexities involved in the management of gastric cancer, I will break down the detailed management strategies based on staging, including surgical options, chemotherapy regimens, and the indications for adjuvant and neoadjuvant therapies.

1. Early-Stage Gastric Cancer (Stage 0, IA, IB)

Staging Overview:

• Stage 0 (Tis N0 M0): Tumor confined to the epithelium (carcinoma in situ).
• Stage IA (T1 N0 M0): Tumor invades the lamina propria or submucosa without lymph node involvement.
• Stage IB (T1 N1 M0 or T2 N0 M0): Tumor invades the lamina propria, muscularis mucosa, or submucosa with 1-2 regional lymph nodes involved, or the tumor invades the muscularis propria without lymph node involvement.

Management Options:

• Surgical Treatment:
  • Endoscopic Mucosal Resection (EMR) and Endoscopic Submucosal Dissection (ESD):
    • Indications:
      • Tumors confined to the mucosa (T1a), less than 2 cm in size, well-differentiated, without ulceration.
      • ESD is preferred for slightly larger tumors (up to 3 cm) or those with minimal submucosal invasion (T1b) in select cases.

  • Gastrectomy:

    • Partial or Total Gastrectomy: Considered for patients with T1b tumors, especially those with lymph node involvement (N1).
    • Lymphadenectomy: D1 or D1+ lymphadenectomy is performed for accurate staging and to reduce recurrence risk. In Subtotal gastrectomy Station 4sa Nodes along Short gastric vessels are preserved. In Total gastrectomy with D2 lymphadenectomy, Station 10 nodes are preserved by japanese these days.

    Pylorus-Preserving Gastrectomy

    Answer: C & D

    Explanation:

    • A. Indicated for T2 lesions: This statement is false. Pylorus-preserving gastrectomy is generally indicated for early-stage gastric cancer (typically T1) that does not involve the deeper layers of the stomach wall, such as T2 lesions. The primary goal is to maintain stomach function and prevent complications like dumping syndrome.
    • B. Right gastric artery is divided: This statement is false. In pylorus-preserving gastrectomy, the right gastric artery is typically preserved to maintain blood supply to the pylorus and the proximal duodenum.
    • C. Lesion should be at least 4 cm from pylorus: This statement is true. For a pylorus-preserving gastrectomy to be effective, the lesion must be located at least 4 cm from the pylorus to ensure clear margins and proper function of the pyloric sphincter.
    • D. Hepatic branch and celiac branch of vagus are preserved: This statement is true. In this procedure, the hepatic and celiac branches of the vagus nerve are preserved to maintain innervation to the liver and gastrointestinal tract, helping to maintain normal digestive function postoperatively.

    

    Summary of Key Points:

    • Pylorus-Preserving Gastrectomy:
      • Indications: Typically for early-stage (T1) gastric cancers that are at least 4 cm away from the pylorus.
      • Vascular Considerations: The right gastric artery is preserved to maintain blood supply.
      • Nerve Preservation: The hepatic and celiac branches of the vagus nerve are preserved to ensure continued function of the liver and GI tract.
    • Adjuvant Therapy:
      • Not typically required for patients with stage 0 or IA who have undergone complete resection with negative margins.
      • For Stage IB: Consider adjuvant chemotherapy, especially if lymph node involvement is detected or the tumor has other high-risk features.

Chemotherapy Regimens:

• Standard Regimens:
  • FLOT (5-FU, Leucovorin, Oxaliplatin, and Docetaxel): Emerging as the preferred regimen for perioperative and adjuvant chemotherapy in early-stage gastric cancer with high-risk features.
  • Capecitabine with Oxaliplatin (CAPOX): Often used as an alternative in the adjuvant setting for patients unable to tolerate FLOT.

2. Locally Advanced Gastric Cancer (Stage IIA, IIB, IIIA, IIIB, IIIC)

Staging Overview:

• Stage IIA (T2 N1 M0 or T3 N0 M0): Tumor invades the muscularis propria with 1-2 regional lymph nodes involved or invades the subserosa without lymph node involvement.
• Stage IIB (T1 N2 M0 or T2 N2 M0 or T3 N1 M0 or T4a N0 M0): Tumor invades various layers with increasing lymph node involvement or invades the serosa without nodal involvement.
• Stage III (T4a or T4b with N1-N3 M0): Tumor invades the serosa or adjacent structures with extensive lymph node involvement.

Management Options:

• Surgical Treatment:
  • Total or Subtotal Gastrectomy:
    • Typically required for tumors invading beyond the submucosa (T2 or higher).
    • D2 Lymphadenectomy: Standard practice, involving removal of perigastric nodes and nodes along the major arteries supplying the stomach.
• Neoadjuvant Therapy:
  • Indications:
    • Strongly recommended for patients with locally advanced disease (T2 or higher, N+).
    • Aims to downstage the tumor, increase the likelihood of a complete resection, and address micrometastatic disease.
  • Regimens:
    • FLOT: Preferred due to its superior outcomes in terms of survival and downstaging compared to older regimens.
    • ECF (Epirubicin, Cisplatin, and 5-FU): Used historically, but largely replaced by FLOT.
    • SOX (S-1 with Oxaliplatin): Considered in Asian populations [ only available in japan and korea, S 1 - is oral 5 FU] or patients intolerant to more intensive regimens.
• Adjuvant Therapy:

  • Postoperative Chemotherapy or Chemoradiotherapy:

    • For Stage II-III: Typically includes continuation of the neoadjuvant regimen (e.g., FLOT).
    • Chemoradiotherapy: Considered especially if there are positive margins or extensive nodal involvement.

  Answer: 1

  Explanation:

  • 1. McDonald regimen consists of giving adjuvant chemoradiotherapy after gastrectomy: This statement is correct. The McDonald regimen involves the administration of adjuvant chemoradiotherapy (5-FU-based) following gastrectomy to improve overall survival and reduce recurrence in patients with gastric cancer.
  • 2. CLASSIC trial involves perioperative Cap-OX chemotherapy: This statement is incorrect. The CLASSIC trial focused on adjuvant chemotherapy with Capecitabine and Oxaliplatin (Cap-OX) after D2 gastrectomy, not perioperative chemotherapy.
  • 3. Adjuvant chemoradiotherapy should be given in node-positive locally advanced gastric cancer: This statement is partially correct but is not the most accurate answer in this context. While adjuvant chemoradiotherapy is often recommended for node-positive, locally advanced gastric cancer, the question's phrasing suggests selecting the most distinct and definitive correct answer.
  • 4. Overall survival of patients in MAGIC trial was greater than FLOT trial: This statement is incorrect. The FLOT trial demonstrated superior overall survival compared to the MAGIC trial, making the FLOT regimen the preferred choice in many cases.

  

Components of FLOT Regimen

Answer: D. Paclitaxel

Summary of Key Points:

• FLOT Regimen Components:
  • 5-FU, Leucovorin, Oxaliplatin, and Docetaxel are the drugs included in the FLOT regimen.
  • Paclitaxel is not a part of the FLOT regimen.

FLOT 4 Trial Overview:

• Study: Conducted by Al-Batran, published in Lancet 2019, RCT in Germany.
• Comparison: FLOT vs. MAGIC (ECF) regimens.
• Patient Group: Resectable cT2/N(+) adenocarcinoma of the gastroesophageal junction (GEJ) and stomach.
• Outcomes: Overall survival was 50 months for the FLOT group vs. 35 months for the MAGIC group, indicating a significant survival benefit with the FLOT regimen.

3. Advanced or Metastatic Gastric Cancer (Stage IV)

Staging Overview:

• Stage IV (Any T, Any N, M1): Presence of distant metastasis, regardless of the primary tumor or nodal involvement.

Management Options:

• Systemic Chemotherapy:
  • First-Line Treatment:
    • FLOT, CAPOX, or EOX (Epirubicin, Oxaliplatin, Capecitabine): Depending on patient tolerance, comorbidities, and performance status.
  • Targeted Therapy:
    • HER2-Positive Tumors: Trastuzumab in combination with chemotherapy (typically cisplatin and 5-FU).
  • Palliative Care: Focuses on symptom management, improving quality of life, and prolonging survival.
• Surgical and Non-Surgical Palliation:
  • Palliative Gastrectomy: Considered for symptom control (e.g., bleeding, obstruction) but generally not curative.
  • Radiation Therapy: Used for local symptom control, such as pain from bony metastases or bleeding.

NCCN Guidelines Specific to Staging:

• Stage-Specific Recommendations:
  • Stage 0-IA: Surgery alone, with careful follow-up.
  • Stage IB-III: Combined modality treatment with surgery, chemotherapy, and in some cases, radiation.
  • Stage IV: Systemic chemotherapy with palliative intent, targeted therapies, and best supportive care.

In the context of the case scenario for Mr. CY, who was staged as pT3N3M0:

• Treatment Strategy:
  • Total Gastrectomy with D2 Lymphadenectomy would be the surgical approach.
  • Adjuvant Chemotherapy with the FLOT regimen is recommended due to the advanced nodal involvement (N3).
  • Surveillance and Follow-up would include regular imaging and endoscopic evaluations to monitor for recurrence.

Case Scenario: Mr. XYZ

MCQ and Explanation

• Answer: B and D
• Explanation:
  • Option B (NACT followed by total gastrectomy + DPS): followed by western population
    • This approach involves using neoadjuvant chemotherapy to reduce tumor size and treat micrometastatic disease, followed by surgery to remove the tumor and involved organs. This is appropriate in cases where the tumor is initially considered borderline resectable.
  • Option D (Total gastrectomy + DPS followed by adjuvant therapy): followed by Japan
    • Another viable strategy involves performing surgery upfront if the tumor is deemed resectable, followed by adjuvant therapy to manage any residual disease and reduce the risk of recurrence.

Resectability and Irresectability Criteria in Gastric Cancer with Multivisceral Involvement

Resectable Scenarios:

• Resection of Adjacent Organs:
  • Distal Pancreas, Spleen, Colon, and Left Lobe of the Liver:
    • These organs can be resected as part of a multivisceral resection if an R0 resection (complete tumor removal with negative margins) is achievable. This aggressive surgical approach is considered when the tumor infiltrates these organs but can still be completely removed.
  • Distal Splenic Artery:
    • Involvement of the distal splenic artery is considered resectable if it allows for a complete resection of the tumor and involved structures.
• Common Organ Involvement:
  • Pancreas, Spleen, and Colon are the three organs most commonly involved in advanced gastric cancer.
  • Multivisceral Resection: If the tumor involves these organs and an R0 resection is feasible, multivisceral resection is performed. However, if the tumor involves the head of the pancreas, a Whipple procedure (pancreaticoduodenectomy) is not typically performed in conjunction with gastrectomy, as the complexity and morbidity are significantly higher.

Irresectable Scenarios:

• Distant Metastasis and Advanced Disease:
  • Distant Metastasis: Presence of distant metastases (e.g., liver deposits, ascites) makes the disease unresectable due to the systemic nature of the spread.
  • Major Vascular Involvement:
    • Proximal Hepatic Artery, Proximal Splenic Artery, Celiac Axis, and Superior Mesenteric Artery (SMA): Tumor involvement of these major vessels generally renders the disease irresectable due to the inability to achieve a complete resection and the high risk of operative morbidity.
• Lymph Node Involvement:
  • Regional Lymph Nodes (Stations 1-12):
    • Lymph nodes from stations 1 to 12 are considered regional and can be resected as part of a curative surgery.
    • Station 12 Lymph Nodes:
      • 12a Nodes (along the Hepatic Artery): These are considered resectable as part of a comprehensive lymphadenectomy.
      • 12b and 12p Nodes: Involvement of these nodes indicates unresectable disease as they are associated with a higher risk of systemic spread.
  • Para-aortic Lymph Nodes:
    • Involvement of para-aortic lymph nodes is a criterion for unresectability, as it indicates a more extensive spread of the disease.
• Other Criteria for Irresectability:
  • Base of the Mesentery, SMA, or SMV Involvement:
    • Tumor involvement at the base of the mesentery or encasement of the SMA or SMV is considered unresectable due to the complexity and risk of achieving negative margins.
  • Hepatoduodenal Ligament Involvement:
    • Involvement of the hepatoduodenal ligament, which contains critical structures like the common bile duct, portal vein, and hepatic artery, is also considered unresectable.

Additional Surgical Considerations:

• Omentectomy:
  • Classical Recommendation: Omentectomy is typically recommended during gastrectomy to reduce the risk of peritoneal spread.
  • Japanese Guidelines: Suggest that in T1 or T2 tumors up to 3 cm from the stomach, a complete omentectomy may not be necessary if the rest of the omentum is left intact, reducing surgical morbidity without compromising oncologic outcomes.
• Bursectomy:
  • Current Practice: Routine bursectomy (removal of the bursa surrounding the stomach) is not commonly performed based on recent guidelines and clinical trials, such as the JCOG trial from Japan, which suggested no significant survival benefit from this procedure in gastric cancer.

Summary of Management Strategies:

• Resectable Cases:
  • Multivisceral resection including organs like the distal pancreas, spleen, colon, or parts of the liver, is feasible if an R0 resection is achievable.
  • Distal splenic artery involvement is resectable, while more proximal vascular involvement typically is not.
  • For lymph nodes, stations 1-12 are resectable, but para-aortic nodes or involvement of nodes beyond 12a indicates unresectability.
• Irresectable Cases:
  • Distant metastasis, major vascular involvement (proximal arteries, SMA), or extensive lymph node involvement (e.g., para-aortic) mark the disease as unresectable.
  • Tumor encasement of the hepatoduodenal ligament or SMA also precludes surgical resection

Lymphadenectomy for Gastric Cancer

Answer: C. 1,3

Explanation:

• 1. D2 lymphadenectomy involves routine removal of spleen and distal pancreas: This statement is false. While D2 lymphadenectomy used to involve routine removal of the spleen and distal pancreas, it is no longer standard practice due to the associated increased perioperative mortality. The current approach avoids routine splenectomy and distal pancreatectomy during D2 dissection to reduce complications.
• 2. Dutch D1 D2 trial showed greater overall survival in D2 lymphadenectomy as compared to D1: This statement is true. The Dutch D1 D2 trial demonstrated that, despite earlier concerns about increased perioperative mortality, D2 lymphadenectomy provides a greater overall survival benefit compared to D1 lymphadenectomy.
• 3. Extended D2 lymphadenectomy improves OS and recurrence-free survival: This statement is false. While D2 lymphadenectomy (stations 1 to 12a) is recommended, further extending the lymphadenectomy to include more nodes (D3 dissection) does not improve overall survival and increases morbidity, making it not a standard recommendation.
• 4. Proximal and distal margin of 4-5 cm is recommended: This statement is true. A proximal and distal margin of 4-5 cm is typically recommended to ensure complete tumor resection with negative margins.

Summary of Key Points:

• 1-12 = regional gastric nodes
• Any other node station as M1
• Extent of lymphadenectomy defined according to type of gastrectomy irrespective of tumor location
• Extent of Lymph Node Dissection:

  • For Total Gastrectomy

    • D1 Lymphadenectomy: Involves removal of perigastric nodes (stations 1 to 7).
    • D1+ Lymphadenectomy = D1 + 8a , 9and 11p
    • D2 Lymphadenectomy: D1+ 8a, 9, 10(not removed), 11p, 11d ,12a. ****Involves removal of nodes along the celiac axis without routine removal of the spleen and distal pancreas.

    • D2+ Lymphadenectomy: if we remove any one of the following nodes along with D2 then it is D2+

      • Station 10 lymph nodes removed if upper stomach invading greater curvature
      • 14v removed if distal stomach with metastasis to station 6 (as Right Gastroepiploic vein drains into SMV)
      • 13 - Posterior PD - invading duodenum
      • 16 - Paraaortic lymph node dissection
      • No role of bursectomy

      

    • D3 Lymphadenectomy: Extends dissection to periaortic nodes (stations 1 to 16) but is not recommended due to increased morbidity without survival benefit.

      • Distal Subtotal gastrectomy = 4sa , 10 and 11d are not removed
    • D0 - anything less than D1
    • D1 - 1, 3, 4sb, 4d, 5,6 and 7
    • D1+: D1+ 8a and 9
    • D2: D1 + 8a,9, 11p and 12a
      • Tumors involving distal esophagus
    • D1+: includes 110
    • D2: 19,20 and 111
    • Dutch D1 D2 Trial: Demonstrated improved survival with D2 dissection compared to D1, but routine splenectomy and distal pancreatectomy are no longer performed due to high perioperative mortality.
    • Current Guidelines: D2 dissection is recommended by NCCN and European Society for Medical Oncology for curative intent surgeries.
    • Margin Recommendations: Proximal and distal resection margins of 4-5 cm are typically recommended to achieve clear margins.

RECOMENDATIONS: Japanese Gastric Cancer Treatment Guidelines 2014 Gastric cancer(2017)

• D1: T1a tumors do not meet criteria for endoscopic resection; T1bN0 less than 1.5cm, well differentiated
• D1+: cT1NO tumors other than above
• D2: T2-T4 / cTN+, • Splenectomy only when direct involvement of tumor (JCOG 0110)

Dutch D1D2 trial:

• 15 year survival data (2010) SWAYED evidence towards D2 lymphadenectomy
• Gastric cancer related deaths significantly higher in D1(48%) group vs D2(37%) (P=0.01)
• Locoregional recurrence higher in D1 group(40.7%) vs 21.8% in D2 group (P=0.01)
• Overall survival was similar 21% in D1 and 29% in D2
• Excluding postoperative death overall survival (25% D1 vs 35% D2 P=0.08)
• Pancreatectomy and splenectomy lowered overall survival
• Spleen preserving D2 dissection as standard of care for resectable gastric cancer

MRC trial:

• Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial THE LANCET
• Multicentric trial randomized 400 patients in two arms : D1(200) and D2 (200) •
• Omental bursectomy; distal pancreaticosplenectomy for middle and upper third lesions •
• Hepatoduodenal and retroduodenal nodes (antral regions) •
• D2 lymphadenectomy had higher postoperative complications (46% vs 28% p<0.001), postoperative mortality (13 vs 6.5% P=0.004) •
• 5 year survival was similar (35% D1 and 33% for D2(6.5 year), as was recurrence free and gastric cancer specific survival

Adjuvant and Neoadjuvant therapies in Gastric Cancer from SKF and Sabiston:

SKF

Multimodality Therapy in Gastric Cancer: Key Points for Revision

General Overview:

• Multimodality Therapy:
  • Improves survival in patients with stage IB or higher gastric cancer.
  • Includes perioperative chemotherapy, preoperative chemoradiation, and postoperative chemotherapy or chemoradiation.
• Macdonald Protocol:
  • Adjuvant chemoradiotherapy using 5-fluorouracil (5-FU).
  • Demonstrates significant improvement in overall survival and disease-free survival.
  • Consideration of patient factors (tolerance to radiation) and tumor-specific factors (nodal involvement, tumor location).
• MAGIC Trial Protocol:
  • Pre- and postoperative chemotherapy for resectable gastric cancers.
  • Shows significant improvement in overall survival and disease-free survival.
  • Aggressive neoadjuvant protocol should be individualized based on patient factors.
• Institutional Variation:
  • Treatment approaches for gastric cancer may vary significantly.
  • Treatment plans should be developed in a multidisciplinary setting.

Neoadjuvant Therapy:

MAGIC Trial:

• Evaluated pre- and postoperative chemotherapy in stage II or higher gastroesophageal cancers.
• Chemotherapy Regimen: 5-FU, epirubicin, and cisplatin.
• Significant improvement in 5-year survival (36% vs. 23%, P = .009) compared to surgery alone.
• Demonstrated tumor downstaging and decrease in local recurrence rates.
• Completion Rates: Less than 50% of patients completed all chemotherapy cycles, highlighting the importance of preoperative chemotherapy.

ACCORD 07 Trial:

• Showed downsizing of tumor and nodal stages with pre- and postoperative chemotherapy.
• Similar outcomes to the MAGIC trial in terms of survival and downstaging.

Adjuvant Therapy:

• General Overview:
  • Adjuvant chemotherapy is strongly advocated following surgical resection despite modest results from multiple trials.
• GASTRIC Group Evaluation:
  • Evaluated 31 trials showing a modest advantage in overall survival and disease-free survival with adjuvant chemotherapy.
  • Challenges: Underpowered studies with various chemotherapeutic agents.

CLASSIC Trial:

• Proposed the use of postoperative chemotherapy with capecitabine and oxaliplatin.
• Showed significant improvement in disease-free survival across all stages.
• Treatment was performed in conjunction with a D2 lymphadenectomy.
• Radiation Therapy:
  • Gastric cancer is generally radioresistant, and radiation therapy is rarely indicated.

> **Macdonald Protocol**: Combines 5-FU-based chemotherapy and radiation.
> 
> - Improves disease-free and overall survival.
> - Criticized for lack of appropriate lymphadenectomy (over half of patients had less than a D1 resection).
> - Despite criticisms, adjuvant chemoradiation is recommended due to significant survival benefits.

• Recurrence and Peritoneal Carcinomatosis:
  • Common Recurrence: Peritoneal cavity is a frequent site for gastric adenocarcinoma recurrence.
  • Systemic Chemotherapy: Poor response rates with peritoneal carcinomatosis.
  • Cytoreductive Surgery and Intraperitoneal Chemotherapy:
    • Studied in select patients with mixed results.
    • Currently not recommended as the standard of care.

Sabiston:

Adjuvant and Neoadjuvant Therapy in Gastric Cancer: Key Points for Revision

Overview of Gastric Cancer Recurrence:

• High Recurrence Rates: Gastric cancer is biologically aggressive, with high recurrence and subsequent mortality rates.
• Types of Recurrence: Most common recurrences are distant or peritoneal; locoregional recurrence occurs in 10-20% of cases.
• Prognosis: Poor prognosis for patients with recurrence, leading to focus on preventing recurrence through neoadjuvant and adjuvant therapies.

Adjuvant Therapy:

• Southwest Oncology Group (9008/INT-0116) Trial:
  • Study Design: Randomized controlled trial of 556 patients undergoing curative gastrectomy alone or with adjuvant 5-FU and radiotherapy.
  • Results: Significant benefit for adjuvant therapy in overall survival (41% vs. 50%) and recurrence-free survival (41% vs. 64%).
  • Criticisms: High rate of inadequate lymphadenectomy (54% had D0 resection), potential benefit from radiation clearing residual disease in perigastric nodes.
  • Completion Rates: Only 64% of patients in the treatment arm completed therapy; 17% stopped due to toxic effects, and 5% progressed during treatment.
• CLASSIC Trial:
  • Study Design: Randomized 1035 patients to surgery alone or surgery followed by eight 3-week cycles of capecitabine plus oxaliplatin.
  • Results: Improved 5-year disease-free survival (68% vs. 53%) and overall survival (78% vs. 69%) with adjuvant chemotherapy.
  • Completion Rates: 67% of patients in the chemotherapy group received all eight cycles as planned.
• Meta-Analyses and Common Regimens:
  • Survival Benefit: Meta-analyses support a survival benefit of adjuvant chemotherapy after complete oncologic resection for patients with greater than pathologic T2N0 disease.
  • Common Regimens: Include ECF (epirubicin, cisplatin, 5-FU), CAPOX (capecitabine, oxaliplatin), and FOLFOX (5-FU, leucovorin, oxaliplatin).
• Adjuvant Radiotherapy:
  • Debated Benefit: Less clear benefit, with theoretical advantages due to high rates of local recurrence and nodal disease.
  • INT-0116 Trial: Showed benefit to chemoradiation, though partly due to inadequate lymphadenectomy.
  • ARTIST Trial: No difference in outcomes between adjuvant chemotherapy alone vs. chemotherapy plus radiotherapy. However, subgroup analysis suggested improved disease-free survival with radiotherapy in patients with lymph node metastases.
  • Current Recommendation: Consider adjuvant radiotherapy for patients with less than D2 lymphadenectomy and positive nodal disease.

Neoadjuvant Therapy:

• MAGIC Trial:
  • Study Design: Randomized 503 patients with stage II or higher gastroesophageal cancer to perioperative chemotherapy (ECF) vs. surgery alone.
  • Completion Rates: Over 90% completed preoperative chemotherapy, but only 50% completed both pre- and postoperative chemotherapy.
  • Results: Significantly better pathologic outcomes and long-term survival with perioperative chemotherapy.
  • Outcomes: Higher percentage of T1/T2 tumors and limited nodal disease (N0/N1) in final specimens; improved 5-year overall survival (36.3% vs. 23%) and lower rates of local recurrence and distant metastases.
• FLOT4 Study:
  • Comparison: Compared MAGIC trial regimen (ECF) to four preoperative and four postoperative cycles of FLOT (docetaxel, oxaliplatin, leucovorin, 5-FU).
  • Results: Significantly better median overall survival (50 vs. 35 months, P = 0.012) and progression-free survival (30 vs. 18 months, P = 0.004) with the FLOT regimen.

Current and Future Research:

• Ongoing Research: The optimal chemotherapy regimen, timing of therapy, and role of radiotherapy for operable gastric cancer are still under investigation.
• Emerging Therapies: Targeted treatments and immunotherapy show promise in advanced/systemic disease and may be integrated into regimens for resectable gastric cancer in the future.

Palliative Therapy and Systemic Therapy in Gastric Cancer: Key Points for Revision

Overview:

• Unresectable or Metastatic Gastric Cancer:
  • Accounts for almost 50% of patients presenting with the disease.
  • Median survival with best supportive therapy: 3-5 months.
  • Many patients are asymptomatic, but those with debilitating symptoms should be considered for palliative surgical therapy even in the presence of metastatic disease.

Common Complications and Management:

• Bleeding:
  • Acute bleeding can be treatment-related or due to the tumor.
  • Management:
    • Endoscopic assessment and control (initial success and recurrent bleeding rates are suboptimal).
    • Angiographic embolization or external beam radiation therapy for persistent bleeding.
• Nausea and Vomiting:
  • Common symptoms, should be treated with antiemetic therapy.
  • Assessment: Evaluate for luminal obstruction.
• Obstruction:
  • Management Options:
    • Placement of an endoscopic enteral stent.
    • Radiation therapy or systemic chemotherapy to shrink the obstructing tumor.
    • Surgical intervention (gastrojejunostomy or palliative gastrectomy in select patients).
    • Venting gastrostomy tube if obstruction cannot be alleviated.
• Perforation:
  • Requires surgical intervention.
  • Management:
    • Closure with healthy omentum is a reasonable approach.
    • Gastrectomy may be performed if it can be done without excess morbidity.

Systemic Chemotherapy:

• Improves Survival: Prognosis remains poor with median survival of less than a year.
• Standard Doublet Regimens: 5-FU and a platinum agent (cisplatin or oxaliplatin).
• Triplet Regimens: Reserved for patients who are medically fit, have good performance status, and access to frequent toxicity evaluation.
• NCCN Guidelines:
  • Recommend doublet regimens as standard.
  • Triplet regimens for selected patients.

Targeted Therapies:

• HER2 Inhibitors:
  • HER2 Positivity: Reported in about 20% of gastric cancers.
  • ToGA Trial: Evaluated capecitabine or 5-FU with cisplatin and trastuzumab vs. cisplatin alone.
    • Better median survival in trastuzumab group (13.8 vs. 11.1 months).
    • HER2 testing recommended for all metastatic gastric cancer patients at diagnosis.
• Other Targeted Therapies:
  • Cetuximab: Epidermal growth factor receptor inhibitor.
  • Ramucirumab and Bevacizumab: Vascular endothelial growth factor inhibitors.
  • Nivolumab and Pembrolizumab: Immunotherapy showing modest survival improvements in advanced disease.

Outcomes:

• Declining Mortality and Incidence: Likely due to dietary changes, food storage and preparation, decreased smoking, and improved treatment options.
• 5-Year Survival Rates:
  • Overall: ~30%.
  • Locally advanced or distant disease: >63% not candidates for surgery.
  • Curative resection: 25%-75%.
  • Early gastric cancer: >80% cure rates.
  • Distant disease: 5% long-term survival.

Recurrence:

• High Recurrence Rates: 30%-90%, most within the first 2 years.
• Most Common reccurence = Distant or peritoneal
• Locoregional Recurrence: ~40%.
  • Common sites: Gastric remnant at anastomosis, gastric bed, regional nodal basins.
• Systemic Recurrence: Predominantly liver and peritoneum.

Surveillance:

• NCCN Recommendations:
  • History and Physical Examination:
    • Every 3-6 months for 1-2 years.
    • Every 6-12 months for 3-5 years.
    • Annually thereafter.
  • Laboratory Tests: Complete blood count and liver function tests as clinically indicated.
  • Imaging: CT or PET/CT scans if there is clinical suspicion of recurrence.
  • Endoscopy: Annual endoscopy for patients who had subtotal gastrectomy or endoscopic resection.